Hertzel C Gerstein1,2,3, Guillaume Pare2,3,4,5, Sibylle Hess6, Rebecca J Ford7, Jennifer Sjaarda2, Kripa Raman2, Matthew McQueen2, ShunFu Lee2,3, Heinz Haenel6, Gregory R Steinberg7,8. 1. Department of Medicine, McMaster University, Hamilton, Ontario, Canada gerstein@mcmaster.ca. 2. Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada. 3. Hamilton Health Sciences, Hamilton, Ontario, Canada. 4. Department of Pathology, McMaster University, Hamilton, Ontario, Canada. 5. Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada. 6. Research and Development Diabetes, Sanofi Aventis Deutschland GmbH, Frankfurt, Germany. 7. Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 8. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Abstract
OBJECTIVE: Metformin is a commonly used glucose-lowering drug. However, apart from glycemic measures, no biomarker for its presence or dose has been identified. RESEARCH DESIGN AND METHODS: A total of 237 biomarkers were assayed in baseline serum from 8,401 participants (2,317 receiving metformin) in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. Regression models were used to identify biomarkers for metformin use. RESULTS: Growth differentiation factor 15 (GDF15) was strongly linked to metformin, such that the odds of metformin use per SD increase in level varied from 3.73 (95% CI 3.40, 4.09) to 3.94 (95% CI 3.59, 4.33) depending on the other included variables. For the remaining 25 linked biomarkers, the odds ranged from 0.71 to 1.24. A 1.64 ng/mL higher GDF15 level predicted a 188-mg higher metformin dose (P < 0.0001). CONCLUSIONS: GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin.
OBJECTIVE:Metformin is a commonly used glucose-lowering drug. However, apart from glycemic measures, no biomarker for its presence or dose has been identified. RESEARCH DESIGN AND METHODS: A total of 237 biomarkers were assayed in baseline serum from 8,401 participants (2,317 receiving metformin) in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. Regression models were used to identify biomarkers for metformin use. RESULTS:Growth differentiation factor 15 (GDF15) was strongly linked to metformin, such that the odds of metformin use per SD increase in level varied from 3.73 (95% CI 3.40, 4.09) to 3.94 (95% CI 3.59, 4.33) depending on the other included variables. For the remaining 25 linked biomarkers, the odds ranged from 0.71 to 1.24. A 1.64 ng/mL higher GDF15 level predicted a 188-mg higher metformin dose (P < 0.0001). CONCLUSIONS:GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin.
Authors: Marta Díaz; Gemma Carreras-Badosa; Joan Villarroya; Aleix Gavaldà-Navarro; Judit Bassols; Francis de Zegher; Abel López-Bermejo; Francesc Villarroya; Lourdes Ibáñez Journal: Pediatr Res Date: 2022-07-11 Impact factor: 3.953
Authors: Jie Zheng; Min Xu; Venexia Walker; Jinqiu Yuan; Roxanna Korologou-Linden; Jamie Robinson; Peiyuan Huang; Stephen Burgess; Shiu Lun Au Yeung; Shan Luo; Michael V Holmes; George Davey Smith; Guang Ning; Weiqing Wang; Tom R Gaunt; Yufang Bi Journal: Diabetologia Date: 2022-07-29 Impact factor: 10.460
Authors: Emily A Day; Rebecca J Ford; Brennan K Smith; Pedrum Mohammadi-Shemirani; Marisa R Morrow; Robert M Gutgesell; Rachel Lu; Amogelang R Raphenya; Mostafa Kabiri; Andrew G McArthur; Natalia McInnes; Sibylle Hess; Guillaume Paré; Hertzel C Gerstein; Gregory R Steinberg Journal: Nat Metab Date: 2019-12-09